The periventricular tissue surrounding the anteroventral third ventricle (AV3V) contains neural tissue critical for normal water and electrolyte metabolism and cardiovascular regulation. Electrolytic ablation of the AV3V region affects thirst, antidiuretic mechanisms, sodium metabolism, pressor responses, and development of hypertension. More recently it has been shown that AV3V ablation results in chronic decreases in plasma volume, and expansion of interstitial fluid volume, but no change in total body water. The specific aims of this research project are: 1) determine which physiological mechanisms of blood volume control are altered acutely and chronically by AV3V ablation; 2) determine if reduced blood volume accounts for attenuated natriuresis in AV3V-lesioned rats; and 3) determine other CNS structures and pathways involved in blood volume regulation. Blood volume and extracellular fluid volume will be measured using radioisotope tracers (125I-albumin and 22Na+) shortly after AV3V lesions or control surgery, and correlated with physiological responses which restore blood volume, such as increased plasma concentrations of renin, corticosterone, and aldosterone. Other experiments are designed to directly measure capillary hydrostatic pressure, pre- and postcapillary resistances, and membrane permeability in the microvasculature of AV3V-lesioned rats. Natriuretic and pressor responses to increased CSF sodium concentration in AV3V-lesioned rats whose plasma volume has been restored will also be measured and compared to responses in control-operated animals. Finally, blood volume and interstitial fluid volume will be measured using radioisotope tracers in animals which have received either electrolytic lesions in other CNS sites, or knife cuts of selected neural pathways which originate in, or course through, the AV3V region. The long term objectives of this research project are to determine the CNS sites and physiological mechanisms which control plasma volume and maintain cardiovascular homeostasis. Understanding the relation between the CNS and cardiovascular homeostasis will increase our knowledge of cardiovascular regulation and mechanisms which may be involved in the development of hypertension.